Stem Cell Transplant Helps Repair Skin in Rare Skin Disease RDEB

There is potentially, good news for patients with a fatal and rare skin disease called recessive dystrophic epidermolysis bullosa (RDEB). Researchers from the University of Minnesota’s Stem Cell Institute report using bone marrow stem cells to successfully repair damaged skin tissue in 7 children with severe RDEB.

RDEB is a painful genetic skin disorder that causes skin to blister and scrape off with the slightest friction or trauma. The injured skin can easily become infected. In severe RDEB, blisters are not confined to the outer skin. They may develop inside the body, in such places as the linings of the mouth, esophagus, stomach, intestines, upper airway, bladder, and genitals.

RDEB is incurable and often fatal disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). According to a National Epidermolysis Bullosa Registry report, 50 epidermolysis bullosa (EB) cases occur per 1 million live births. Of these cases, only approximately 5% are classified as dystrophic EB.

Drs John E. Wagner and colleagues have published their study in the New England Journal of Medicine. They began with the hypothesis that allogeneic marrow might contain stem cells capable of ameliorating the manifestations of RDEB in humans.

The researchers treated seven children who had severe RDEB between October 2007 and August 2009 with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. C7 expression was assessed in the children by means of immunofluorescence staining and transmission electron microscopy to visualize anchoring fibrils. Chimerism was measured by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography.

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One patient died of cardiomyopathy before transplantation. Another patient had severe regimen-related cutaneous toxicity and died at 183 days from graft rejection and infection.

The five patients who survived all had improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation.

The researchers observed increased C7 deposition at the dermal–epidermal junction in five of the six transplant recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies.

The researchers note that further studies are needed to assess long-term risks and benefits.